Project Summary The goal of this SBIR Fast-Track project is to further the commercialization of PathoVax?s bi-valent RGVaxTM as a broad spectrum Human Papillomavirus (HPV) vaccine that targets all clinically relevant HPVs. Current HPV vaccines provide type-restricted protection that focuses only on sexually transmitted HPVs resulting in an unexpected STD stigma that directly affects uptake rates. By targeting additional HPVs especially non-sexual types that causes diseases such as recalcitrant anogenital, cutaneous warts, and life-threatening laryngeal papilloma?s, RGVax? offers the potential to be marketed as a general public health vaccine. This provides the opportunity to sidestep current social stigma and potentially increase market uptake. This unique advantage will attract strategic partners that PathoVax will work with to bring RGVax? into the clinic. PathoVax has licensed the underlying prototype technology based on a HPV virus-like particle (VLP) platform that displays 360 copies of the highly conserved, stable HPV epitope (RG1). Animal vaccination studies utilizing this prototype have confirmed broad-spectrum protection against 27 HPVs, a dramatic improvement over current HPV vaccine that only protects 9 types at best. Given the broad protection, this prototype was awarded an NCI PREVENT grant that supports manufacturing and IND enabling studies. To enhance the odds of market success for this innovation, PathoVax has developed an improved bi-valent RGVaxTM formulation as the final commercial product to satisfy FDA-mandated antibody titer standards and provide comprehensive HPV- disease protection. In this SBIR-Fast Track, Phase 1 specific aims focuses on benchmarking our finalized formulation to obtain competitive profiling data against Gardasil-9, the current standard of care for HPV prevention. This will be done in the same animal models used to validate the current Gardasil vaccine franchise owned by Merck (Aim 1). Once we have demonstrated RGVax?s superiority, we will transition into phase 2 specifics aims whereby PathoVax will demonstrate RGVax?s efficacy data in animal models that simulates immune-suppression, so as to develop pivotal preclinical data to support PathoVax?s clinical strategy by demonstrating RGVaxTM?s ability to prevent skin HPV disease in organ transplant recipients (OTRs) as a first indication for marketing approval (Aim 2). Additionally, PathoVax will provide the FDA with a GMP manufacturing strategy to produce the bi-valent RGVaxTM formulation by working with a vaccine contract manufacturer (CMO) to develop a production and purification process (Aim 3A), and also demonstrate this process produces RGVax vaccine particles that are superior or equivalent to current laboratory produced particles (3B). The timely development of this data package is critical for both our upcoming pre-IND FDA discussion, fund raising to investor groups and initiating our IND-enabling program for a bi-valent phase 1b/2a clinical trial.